tbuckley/cabot-search huggingface dataset:
Association of Childhood and Midlife Neighborhood Socioeconomic Position With Cognitive Decline
Authors: Anna M. Kucharska-Newton, James Russell Pike, Jinyu Chen, Josef Coresh, A. Richey Sharret, Thomas Mosley, Priya Palta
Journal: JAMA Network Open (2023)

Importance Early-life socioeconomic adversity may be associated with poor cognitive health over the life course. Objective To examine the association of childhood and midlife neighborhood socioeconomic position (nSEP) with cognitive decline. Design, Setting, and Participants This cohort study included 5711 men and women enrolled in the community-based Atherosclerosis Risk in Communities (ARIC) Study with repeated cognitive data measured over a median 27.0 years (IQR, 26.0-27.9 years) (1990-2019). Statistical analysis was performed from December 2022 through March 2023. Exposure Residence addresses for ARIC Study cohort participants were obtained at midlife (1990-1993) and as recalled addresses at 10 years of age (childhood). A composite nSEP z score was created as a sum of z scores for US Census–based measures of median household income; median value of owner-occupied housing units; percentage of households receiving interest, dividend, or net rental income; percentage of adults with a high school degree; percentage of adults with a college degree; and percentage of adults in professional, managerial, or executive occupations. Childhood nSEP and midlife nSEP were modeled as continuous measures and discretized into tertiles. Main Outcomes and Measures A factor score for global cognition was derived from a battery of cognitive tests administered at 5 in-person visits from baseline to 2019. The rate of cognitive decline from 50 to 90 years of age was calculated by fitting mixed-effects linear regression models with age as the time scale and adjusted for race, sex, birth decade, educational level, and presence of the apolipoprotein E ε4 allele. Results Among 5711 ARIC Study participants (mean [SD] baseline age, 55.1 [4.7] years; 3372 women [59.0%]; and 1313 Black participants [23.0%]), the median rate of cognitive decline was −0.33 SDs (IQR, −0.49 to −0.20 SDs) per decade. In adjusted analyses, each 1-SD-higher childhood nSEP score was associated with a slower (β, −9.2%; 95% CI, −12.1% to −6.4%) rate of cognitive decline relative to the sample median. A comparable association was observed when comparing the highest tertile with the lowest tertile of childhood nSEP (β, −17.7%; 95% CI, −24.1% to −11.3%). Midlife nSEP was not associated with the rate of cognitive decline. Conclusions and Relevance In this cohort study of contextual factors associated with cognitive decline, childhood nSEP was inversely associated with trajectories of cognitive function throughout adulthood.
Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents
Authors: Kyung Hwa Lee, Jiyoon Shin, Jung Lee, Jae Hyun Yoo, Jae-Won Kim, David A. Brent
Journal: JAMA Network Open (2023)

Importance Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression. Objective To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control. Design, Setting, and Participants This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022. Main Outcomes and Measures Depressive symptoms were assessed using the Children’s Depression Rating Scale–Revised. The outcome measure was defined as the change in Children’s Depression Rating Scale–Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not. Results Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment. Conclusions and Relevance The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.
A global action agenda for turning the tide on fatty liver disease
Authors: Jeffrey V. Lazarus, Henry E. Mark, Alina M. Allen, Juan Pablo Arab, Patrizia Carrieri, Mazen Noureddin, William Alazawi, Naim Alkhouri, Saleh A. Alqahtani, Quentin M. Anstee, Marco Arrese, Ramon Bataller, Thomas Berg, Paul N. Brennan, Patrizia Burra, Graciela E. Castro-Narro, Helena Cortez-Pinto, Kenneth Cusi, Nikos Dedes, Ajay Duseja, Sven M. Francque, Amalia Gastaldelli, Hannes Hagström, Terry T.K. Huang, Dana Ivancovsky Wajcman, Achim Kautz, Christopher J. Kopka, Aleksander Krag, Philip N. Newsome, Mary E. Rinella, Diana Romero, Shiv Kumar Sarin, Marcelo Silva, C. Wendy Spearman, Norah A. Terrault, Emmanuel A. Tsochatzis, Luca Valenti, Marcela Villota-Rivas, Shira Zelber-Sagi, Jörn M. Schattenberg, Vincent Wai-Sun Wong, Zobair M. Younossi
Journal: Hepatology (2023)

Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (&gt; 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.
A Trojan Horse Delivery Vehicle Carrying siRNA Nanotherapeutics with Multiple Tumor Microenvironment Responsiveness Elicits Robust Antitumor Immune Responses In Situ via a “Self‐Synergistic” Approach
Authors: Yan Fang, Shuai Chen, Mingyi Zhang, Xiaojie Lin, Xuechao Jin, Mingming Zhang, Yunmeng Liu, Yaxin Wang, Kai Shi
Journal: Advanced Healthcare Materials (2023)

The potential of small interfering RNAs (siRNAs) in the treatment of malignant tumors has attracted increasing attention due to their inherent advantages. However, their therapeutic performance strongly depends on the efficiency of their cytoplasmic delivery in vivo by the delivery vehicle with good cellular permeability and histocompatibility. Herein, a polycationic carrier camouflaged with macrophage membrane (MPM) is constructed biomimetically, which is condensed from endogenous spermine monomers through diselenide bonds. The developed Trojan horse delivery vehicle has desirable compression efficacy for siRNA oligo against PD-L1 (siPDL1) as well as intracytoplasmic release properties derived from its sequential degradation triggered by redox microenvironment in tumor cells. Furthermore, the coloading of photosensitizer can mediate photodynamic therapy (PDT) accompanied by the generation of reactive oxygen species (ROS) upon light irradiation applied, which accelerated the degradation of the carrier as well as the release of cargoes while enhancing the PD-L1 blockage-mediated immunotherapy by inducing in-situ immunogenic cell death. Moreover, the synchronously delivered siPDL1 attenuated the ROS-induced increase in immunosuppressive PD-L1 expression, thereby effectively eliciting a robust antitumor immune response with a "self-synergistic" manner in the xenograft breast cancer mouse model.
Coronary Plaque Sampling Reveals Molecular Insights Into Coronary Artery Disease
Authors: Michael E. Widlansky, Yong Liu, Shakirah Tumusiime, Benjamin Hofeld, Nabeel Khan, Michael Aljadah, Jingli Wang, Amberly Anger, Qiongzi Qiu, Bhavika Therani, Pengyuan Liu, Mingyu Liang
Journal: Circulation Research (2023)

uch of our understanding of human coronary atherosclerosis is extrapolated from studies of animal models that do not develop coronary atherosclerosis and have limited evidence of plaque instability, or analyses of human coronary atherosclerotic plaques from expired patients or explanted hearts, or peripheral artery plaques.We developed a coronary plaque sampling approach that could be applied broadly in live patients with coronary artery disease to obtain molecular and cellular insights into human coronary atherosclerosis.Our approach combined RNA retrieval directly from balloons used in percutaneous coronary intervention and inexpensive, low-input RNA-Seq using SMART-seq (cost of about $160 for library preparation and sequencing; Figure [A]).The study protocol was approved by the Medical College of Wisconsin's Institutional Review Board.We generated SMART-Seq libraries from coronary samples from 27 patients.The complete dataset is available in the Gene Expression Omnibus (GSE236610).More than 9 million uniquely mapped read pairs were obtained from each library.The median mapping rate was 92%.The median number of genes detected in a library was 30 375, and the interquartile range was 19 651 to 32 973.Of the 27 patients, 13 were confirmed to have stable coronary artery disease (sCAD), and 14 confirmed to have been performed on lesions causing acute coronary syndrome (ACS).Demographic and procedural information was summarized in Figure [B].Patients with ACS met criteria for type 1 myocardial infarction (fourth universal definition).sCAD was defined as exertional anginal symptoms without
Development of a Rare Earth Nanoprobe Enables <i>In Vivo</i> Real-Time Detection of Sentinel Lymph Node Metastasis of Breast Cancer Using NIR-IIb Imaging
Authors: Yuan-Yuan Zhu, Liang Song, Yong-Qu Zhang, Wan-Ling Liu, Wei-Ling Chen, Wen-Liang Gao, Li-Xin Zhang, Jia-Zheng Wang, Zi-He Ming, Yun Zhang, Guo-Jun Zhang
Journal: Cancer Research (2023)

Sentinel lymph node (SLN) biopsy plays a critical role in axillary staging of breast cancer. However, traditional SLN mapping does not accurately discern the presence or absence of metastatic disease. Detection of SLN metastasis largely hinges on examination of frozen sections or paraffin-embedded tissues post-SLN biopsy. To improve detection of SLN metastasis, we developed a second near-infrared (NIR-II) in vivo fluorescence imaging system, pairing erbium-based rare-earth nanoparticles (ErNP) with bright down-conversion fluorescence at 1,556 nm. To visualize SLNs bearing breast cancer, ErNPs were modified by balixafortide (ErNPs@POL6326), a peptide antagonist of the chemokine receptor CXCR4. The ErNPs@POL6326 probes readily drained into SLNs when delivered subcutaneously, entering metastatic breast tumor cells specifically via CXCR4-mediated endocytosis. NIR fluorescence signals increased significantly in tumor-positive versus tumor-negative SLNs, enabling accurate determination of SLN breast cancer metastasis. In a syngeneic mouse mammary tumor model and a human breast cancer xenograft model, sensitivity for SLN metastasis detection was 92.86% and 93.33%, respectively, and specificity was 96.15% and 96.08%, respectively. Of note, the probes accurately detected both macrometastases and micrometastases in SLNs. These results overall underscore the potential of ErNPs@POL6326 for real-time visualization of SLNs and in vivo screening for SLN metastasis.NIR-IIb imaging of a rare-earth nanoprobe that is specifically taken up by breast cancer cells can accurately detect breast cancer macrometastases and micrometastases in sentinel lymph nodes.
Time to deterioration of patient-reported outcomes as a surrogate of overall survival: a meta-analysis
Authors: Adel Shahnam, Udit Nindra, Jayesh Desai, Rina Hui, Marc Buyse, Ashley M Hopkins, Michael J Sorich
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Overall survival is the optimal marker of treatment efficacy in randomized clinical trials (RCTs) but can take considerable time to mature. Progression-free survival (PFS) has served as an early surrogate of overall survival but is imperfect. Time to deterioration in quality of life (QOL) measures could be a surrogate for overall survival. Methods Phase 3 RCTs in solid malignancies that reported overall survival, PFS, and time to deterioration in QOL or physical function published between January 1, 2010, and June 30, 2022, were evaluated. Weighted regression analysis was used to assess the relationship between PFS, time to deterioration in QOL, and time to deterioration in physical function with overall survival. The coefficient of determination (R2) was used to quantify surrogacy. Results In total, 138 phase 3 RCTs were included. Of these, 47 trials evaluated immune checkpoint inhibitors and 91 investigated non–immune checkpoint inhibitor agents. Time to deterioration in QOL (137 RCTs) and time to deterioration in physical function (75 RCTs) performed similarly to PFS as surrogates for overall survival (R2 = 0.18 vs R2 = 0.19 and R2 = 0.10 vs R2 = 0.09, respectively). For immune checkpoint inhibitor studies, time to deterioration in physical function had a higher association with overall survival than with PFS (R2 = 0.38 vs R2 = 0.19), and PFS and time to deterioration in physical function did not correlate with each other (R2 = 0). When time to deterioration in physical function and PFS are used together, the coefficient of determination increased (R2 = 0.57). Conclusions Time to deterioration in physical function appears to be an overall survival surrogate measure of particular importance for immune checkpoint inhibitor treatment efficacy. The combination of time to deterioration in physical function with PFS may enable better prediction of overall survival treatment benefit in RCTs of immune checkpoint inhibitors than either PFS or time to deterioration in physical function alone.
Highly pathogenic avian influenza A(H5N1) virus infection on multiple fur farms in the South and Central Ostrobothnia regions of Finland, July 2023
Authors: Erika Lindh, Hanna Lounela, Niina Ikonen, Tuija Kantala, Carita Savolainen-Kopra, Ari Kauppinen, Pamela Österlund, Lauri Kareinen, Anna Katz, Tiina Nokireki, Jari Jalava, Laura London, Marjaana Pitkäpaasi, Jaana Vuolle, Anna-Liisa Punto-Luoma, Riikka Kaarto, Liina Voutilainen, Riikka Holopainen, Laura Kalin-Mänttäri, Terhi Laaksonen, Hannu Kiviranta, Aino Pennanen, Otto Helve, Ilona Laamanen, Merit Melin, Niina Tammiranta, Ruska Rimhanen-Finne, Tuija Gadd, Mika Salminen
Journal: Eurosurveillance (2023)

Since mid-July 2023, an outbreak caused by highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b genotype BB is ongoing among farmed animals in South and Central Ostrobothnia, Finland. Infections in foxes, American minks and raccoon dogs have been confirmed on 20 farms. Genetic analysis suggests introductions from wild birds scavenging for food in farm areas. Investigations point to direct transmission between animals. While no human infections have been detected, control measures are being implemented to limit spread and human exposure.
Comparison of SARS-CoV-2 Hyperimmune Immunoglobulins Following Infection Plus Vaccination vs Infection
Authors: Lorenza Bellusci, Hana Golding, Surender Khurana
Journal: JAMA Network Open (2023)

This cross-sectional study compares the neutralizing titers of convalescent plasma and hyperimmune anti–SARS-CoV-2 intravenous immunoglobulins against circulating Omicron subvariants.
Depth of Radiographic Response and Time to Tumor Regrowth Predicts Overall Survival Following Anti-VEGF Therapy in Recurrent Glioblastoma
Authors: Benjamin M. Ellingson, Akifumi Hagiwara, Connor J. Morris, Nicholas S. Cho, Sonoko Oshima, Francesco Sanvito, Talia C. Oughourlian, Donatello Telesca, Catalina Raymond, Lauren E. Abrey, Josep Garcia, Dana T. Aftab, Colin Hessel, Tamar Rachmilewitz Minei, Dror Harats, David A. Nathanson, Patrick Y. Wen, Timothy F. Cloughesy
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Antiangiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In this study, we investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with antiangiogenic therapy. Experimental Design: N = 276 patients in two phase II trials were used as training data, including bevacizumab ± irinotecan (NCT00345163) and cabozantinib (NCT00704288), and N = 74 patients in the bevacizumab arm of a phase III trial (NCT02511405) were used for validation. Enhancing volumes were estimated using T1 subtraction maps, and a biexponential model was used to estimate regrowth (g) and regression (d) rates, time to tumor regrowth (TTG), and the depth of response (DpR). Response characteristics were compared to diffusion MR phenotypes previously shown to predict survival. Results: Optimized thresholds occurred at g = 0.07 months−1 (phase II: HR = 0.2579, P = 5 × 10−20; phase III: HR = 0.2197, P = 5 × 10−5); d = 0.11 months−1 (HR = 0.3365, P &amp;lt; 0.0001; HR = 0.3675, P = 0.0113); TTG = 3.8 months (HR = 0.2702, P = 6 × 10−17; HR = 0.2061, P = 2 × 10−5); and DpR = 11.3% (HR = 0.6326, P = 0.0028; HR = 0.4785, P = 0.0206). Multivariable Cox regression controlling for age and baseline tumor volume confirmed these factors as significant predictors of survival. Patients with a favorable pretreatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth. Conclusions: Recurrent glioblastoma patients with a large, durable radiographic response to antiangiogenic agents have significantly longer survival. This information is useful for interpreting activity of antiangiogenic agents in recurrent glioblastoma.
MFSD2A potentiates gastric cancer response to anti‐PD‐1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response
Authors: Bin Zhang, Chun‐Mei Wang, Hao‐Xiang Wu, Feng Wang, Yang‐Yang Chai, Ye Hu, Bing‐Jing Wang, Zhou Yu, Rong‐Hua Xia, Rui‐Hua Xu, Xue‐Tao Cao
Journal: Cancer Communications (2023)

The efficacy of anti-programmed cell death protein 1 (PD-1) immunotherapy in various cancers, including gastric cancer (GC), needs to be potentiated by more effective targeting to enhance therapeutic efficacy or identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting or/and promoting anti-PD-1 therapeutic response in advanced GC (AGC).The transcriptome of AGC tissues from patients with different clinical responses to anti-PD-1 immunotherapy and GC cells was analyzed by RNA sequencing. The protein and mRNA levels of the major facilitator superfamily domain containing 2A (MFSD2A) in GC cells were assessed via quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. Additionally, the regulation of anti-PD-1 response by MFSD2A was studied in tumor-bearing mice. Cytometry by Time-of-Flight, multiple immunohistochemistry, and flow cytometry assays were used to explore immunological responses. The effects of MFSD2A on lipid metabolism in mice cancer tissue and GC cells was detected by metabolomics.Higher expression of MFSD2A in tumor tissues of AGC patients was associated with better response to anti-PD-1 immunotherapy. Moreover, MFSD2A expression was lower in GC tissues compared to adjacent normal tissues, and its expression was inversely correlated with GC stage. The overexpression of MFSD2A in GC cells enhanced the efficacy of anti-PD-1 immunotherapy in vivo by reprogramming the tumor microenvironment (TME), characterized by increased CD8+ T cell activation and reduced its exhaustion. MFSD2A inhibited transforming growth factor β1 (TGFβ1) release from GC cells by suppressing cyclooxygenase 2 (COX2)-prostaglandin synthesis, which consequently reprogrammed TME to promote anti-tumor T cell activation.MFSD2A potentially serves as a predictive biomarker for anti-PD-1 immunotherapy response in AGC patients. MFSD2A may be a promising therapeutic target to potentiate the efficacy of anti-PD-1 immunotherapy by reprogramming the TME to promote T cells activation.